92-67-1

Usage

Production Methods

Because of its carcinogenic effects, 4-aminobiphenyl has not been produced commercially in the United States since the mid 1950s (Koss et al. 1969). It was present in the drug and cosmetic color additive D&C yellow no. 1; however, use of this color additive was discontinued in the late 1970s (HSDB 2009). 4-Aminobiphenyl has beenreported to be formed by the decomposition of 1,3-diphenyltriazeneproduced by the reaction of diazoaniline and aniline during manufacture of the dye D&C red no. 33 (Bailey 1985). In 2009, 4-aminobiphenyl (for use in research) was available from 11 U.S. suppliers, including one company that supplied bulk quantities (ChemSources 2009). 4-Aminobiphenyl also has been reported as a contaminant in diphenylamine (HSDB 2009).

Synthesis Reference(s)

Journal of the American Chemical Society, 97, p. 7184, 1975 DOI: 10.1021/ja00857a049Tetrahedron Letters, 39, p. 1313, 1998 DOI: 10.1016/S0040-4039(97)10877-2

Air & Water Reactions

Is oxidized by air (darkens on oxidation). Insoluble in water.

Reactivity Profile

4-AMINOBIPHENYL is a weak base. Incompatible with acids and acid anhydrides. Forms salts with hydrochloric acid and sulfuric acid. Can be diazotized, acetylated and alkylated. . May react with strong oxidizing agents.

Hazard

Toxic by ingestion, inhalation, skin absorp- tion. Confirmed carcinogen. Bladder and liver can- cer.

Health Hazard

4-Aminodiphenyl exposure is associated with a high incidence of bladder cancer in humans.

Fire Hazard

4-AMINOBIPHENYL is probably combustible.

Safety Profile

Confirmed human carcinogen with experimental carcinogenic and tumorigenic data. Poison by ingestion and intraperitoneal routes. Human mutation data reported. An irritant. Effects resemble those of benzidine. See also BENZIDINE. Slight to moderate fire hazard when exposed to heat, flames (sparks), or powerful oxidzers. To fight fire, use water spray, mist, dry chemical. When heated to decomposition it emits toxic fumes of NOx,. See also AROMATIC AMINES.

Potential Exposure

4-Aminobiphenyl is no longer manufactured commercially and is only used for research purposes. 4-Aminobiphenyl was formerly used as a rubber antioxidant and as a dye intermediate. Is a contaminant in 2-aminobiphenyl.

Carcinogenicity

4-Aminobiphenyl is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans. Cancer of the urinary bladder was first reported to be associated with occupational exposure to 4-aminobiphenyl in a descriptive epidemiological study (published in the mid 1950s), in which 11% (19 of 171) of workers in a plant manufacturing 4-aminobiphenyl developed urinary-bladder cancer. These workers had been exposed to 4-aminobiphenyl for 1.5 to 19 years between 1935 and 1955. Publication of this study led to an effort to discontinue production and useof 4-aminobiphenyl. Starting in 1955, 541 workers who had been exposed to 4-aminobiphenyl were followed for an additional 14 years; 43 men (7.9%) developed histologically confirmed urinary-bladder cancer. In a survey of workers at a plant producing a variety of chemicals, the risk of mortality from urinary-bladder cancer was elevated tenfold, and all of the men who died of urinary-bladder cancer had worked at the plant during the period when 4-aminobiphenyl was used (1941 through 1952). The International Agency for Research onCancer concluded that there was sufficient evidence of the carcinogenicity of 4-aminobiphenyl in humans (IARC 1972, 1987). Since 4-aminobiphenyl was listed in the First Annual Report on Carcinogens, most research on its carcinogenicity has focused on exposure from cigarette smoking. Epidemiological studies have reported the incidence of urinary-bladder cancer to be 2 to 10 times as high among cigarette smokers as among nonsmokers. Higher levels of 4-aminobiphenyl adducts (4-aminobiphenyl metabolites bound to DNA or protein) were detected in bladder tumors (DNA adducts) and red blood cells (hemoglobin adducts) from smokers thanfrom nonsmokers (Feng et al. 2002). In a case-control study, levels of 4-aminobiphenyl–hemoglobin adducts were higher in smokers with urinary-bladder cancer than in a control group of similarly exposed smokers (Del Santo et al. 1991). A Taiwanese study reported that 4-aminobiphenyl–hemoglobin adducts were associated with increased risk of liver cancer (Wang et al. 1998).

Environmental Fate

4-Aminobiphenyl is one of a number of chemicals that cause methemoglobinemia, or conversion of hemoglobin to methemoglobin, which reduces the ability of the blood to carry oxygen to the tissues. In addition, the active metabolite is believed to produce cancer through its reaction with cellular DNA. In animal studies, the observed incidence of 4-aminobiphenyl adducts with bladder epithelium DNA correlated well with the observed bladder tumor incidence.

Metabolic pathway

Ring oxidation of 4-aminobiphenyl occurred only to a minor extent in microsomes. In contrast, N-oxidation of 4,4'-methylene-bis-(2-chloroaniline) is preferentially catalyzed by the phenobarbital-induced enzymes P- 450PB-B and P-450PB-D to cause ring oxidation and methylene carbon oxidation. 4,4'-Methylene-bis-(2- chloroaniline) ring oxidation and methylene carbon oxidation show varied cytochrome P-450 selectivity and accounted for 14-79% of total oxidation products.

Purification Methods

Crystallise it from water or EtOH. [Beilstein 12 IV 3241.] CARCINOGENIC.

Toxicity evaluation

4-Aminobiphenylmay have been released into the environment during its production and use as a rubber antioxidant and dye intermediate; however, sources suggest that it was no longer in significant production by the early 1970s. 4-Aminobiphenyl is easily oxidizable and probably undergoes photolysis but there is little actual data on these processes. If released on land it is expected to adsorb moderately to soil, probably binding to humic materials, and undergo redox reactions. If released to surface water, it is expected to adsorb to sediment, and probably undergo photolysis and oxidation. It may be degraded by oxidation by alkoxy radicals, which are photochemically produced in eutrophic waters, with an estimated half-life of 14 days. 4-Aminobiphenyl is biodegradable and biodegradation may well occur in both soil and water but there are no rates available for soil or surface waters. It has a low potential for bioconcentration. In the atmosphere, degradation should occur due to direct photolysis, oxidation by ambient oxygen, and photochemically produced hydroxyl radicals (estimated half-life 6–7 h in the vapor phase).

Incompatibilities

Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides and acid anhydrides.

Waste Disposal

Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposal. Controlled incineration whereby oxides of nitrogen are removed from the effluent gas by scrubber, catalytic or thermal devices.

InChI:InChI=1/C12H11N/c13-12-8-6-11(7-9-12)10-4-2-1-3-5-10/h1-9H,13H2

Upstream product

• 5957-03-9 Diphenyl-4,4'-bis-diazonium 
• 92-93-3 1-phenyl-4-nitrobenzene 
• 492-17-1 2,4'-diaminobiphenyl 
• 6810-26-0 4-hydroxylaminobiphenyl 
• 98-95-3 nitrobenzene 
• 71-43-2 benzene 
• 62-53-3 aniline 
• 622-37-7 Phenyl azide 
• 297766-64-4 1,3-Diphenyltriazen 
• 1227476-15-4 Azobenzene 
• 2051-62-9 4'-biphenyl chloride 
• 5326-53-4 1,2-di([1,1'-biphenyl]-4-yl)diazene 
• 25288-76-0 3-aminodibenzothiophene 
• 92-52-4 biphenyl 

Downstream Products

• 339159-93-2 N-biphenyl-4-yl-maleamic acid 
• 76656-10-5 3-methyl-thiophene-2-carboxylic acid biphenyl-4-ylamide 
• 1592-49-0 2-([1,1'-biphenyl]-4-yl)isoindoline-1,3-dione 
• 856357-68-1 2-(4-aminophenyl)anthracene-9,10-dione 
• 861079-64-3 2-(4'-amino-biphenyl-4-carbonyl)-benzoic acid 
• 6629-43-2 N-(biphenyl-4-ylamino-methyl)-phthalimide 
• 102024-11-3 piperonal-biphenyl-4-ylimine 
• 103167-49-3 acridin-9-ylmethylene-biphenyl-4-yl-amine 
• 68888-26-6 6-biphenyl-4-ylamino-3-methyl-3H-naphtho[1,2,3-de]quinoline-2,7-dione 
• 92-95-5 4-biphenyl isocyanate 
• 63039-93-0 9-phenyl-benz[c]acridine 
• 4432-94-4 N,N-bis(phenyl)-4-biphenylamine 
• 1510-24-3 1-isothiocyanato-4-phenylbenzene 
• 95820-74-9 biphenyl-4-yl-fluoren-9-yliden-amine 

Relevant academic research and scientific papers

Turning on Catalysis: Construction of Triphenylphosphine Moieties into Porous Frameworks

In this work, we present an effective strategy to enhance the reactivity and durability of molecular organometallic catalysts by constructing into porous frameworks, as demonstrated by triphenylphosphine (PPh3). Such PPh3 moieties accessible via the porous structures could be partially metalated by Pd species to generate a highly efficient and recyclable heterogeneous catalyst for the Suzuki coupling of aryl chlorides. Site isolation in the rigid framework stabilizes the catalytically active monophosphine-ligated complex against deactivation into less active assemblies of bisphosphine-Pd. Meanwhile, the densely populated free ligands inhibit the decomposition of catalytically active sites thereby highlighting the beneficial effects of such a platform. Thus, the tunability of porous polymer synthesis gives great promise to impart numerous organometallic catalysts constituted by readily available ligands with unique reactivity, which are not trivially achievable with traditional systems.

Phosphine-Based Covalent Organic Framework for the Controlled Synthesis of Broad-Scope Ultrafine Nanoparticles

In this work, a phosphine-based covalent organic framework (Phos-COF-1) is successfully synthesized and employed as a template for the confined growth of broad-scope nanoparticles (NPs). Ascribed to the ordered distribution of phosphine coordination sites in the well-defined pores, various stable and well-dispersed ultrafine metal NPs including Pd, Pt, Au, and bimetallic PdAuNPs with narrow size distributions are successfully prepared as determined by transmission electron microscopy, X-ray photoelectron spectroscopy, inductively coupled plasma, and powder X-ray diffraction analyses. It is also demonstrated that the as-prepared Phos-COF-1-supported ultrafine NPs exhibit excellent catalytic activities and recyclability toward the Suzuki–Miyaura coupling reaction, reduction of nitro-phenol and 1-bromo-4-nitrobenzene, and even tandem coupling and reduction of p-nitroiodobenzene. This work will open many new possibilities for preparing COF-supported ultrafine NPs with good dispersity and stability for a broad range of applications.

Template-less synthesis of polymer hollow spheres: An efficient catalyst for Suzuki coupling reaction

We report here a method for the preparation of polymer hollow spheres in which 3-aminoquinoline (3-AQ) and palladium acetate were used as precursors. During the reaction 3-AQ was oxidized and formed poly(3-AQ). IR and Raman spectra provided information on the chemical structure of the polymer. The oxidation state of palladium was confirmed by X-ray photoelectron spectroscopic analysis. Transmission and scanning electron microscopy were used to determine the size and morphology of the polymer. The palladium-poly(3-AQ) supramolecular system was used as an effective catalyst for the Suzuki coupling reaction of aryl halides in the absence of a phosphine ligand. Copyright

Suzuki cross-coupling of aryl halides with phenylboronic acid catalysed by an amidoxime fibres-nickel(0) complex

Amidoxime fibres-nickel(0) complexes [Ni(0)-AOFs] were synthesised by combining a Ni2+-solution with amidoxime fibres and reduced by NaH 2PO2. The Ni(0)-AOFs are inexpensive phosphine-free recyclable heterogeneous catalysts for the Suzuki coupling reaction of aryl halides with phenylboronic acid to provide the corresponding biphenyls in high yields. The heterogeneous catalyst can be readily recovered by simple filtration and reused several times without significant loss of activity.

Photoinduced intramolecular charge transfer in diphenylamino-substituted triphenylbenzene, biphenyl, and fluorene

The photophysical properties of a diphenyl amino-substituted triphenylbenzene, (pEFTP), biphenyl (pEFBP), and fluorene (pEFF) derivative are compared. The similarity of the photophysical properties and their solvent dependence for the triphenylbenzene and the biphenyl model compound indicate the formation of a polar excited state, localized in one branch of pEFTP. Further comparison with the fluorene model compound suggests an excited state relaxation process of the biphenyl moiety in solvents of medium and high polarity toward a more planar geometry. The depopulation of the excited state is explained in the framework of the model developed to rationalize the photophysics of substituted biphenyl.

In situ biosynthesis of palladium nanoparticles on Artemisia abrotanum extract-modified graphene oxide and its catalytic activity for Suzuki coupling reactions

We progressed the catalytic activity of Pd NPs coated on Artemisia abrotanum extract-modified graphene (Pd NPs/RGO) for the Suzuki coupling reactions. Pd NPs/RGO nanocatalyst was fabricated via modifying the surface of graphene oxide (GO) with A. abrotanum extract as a reducing and stabilizing agent with no addition of any toxic agent to in situ reduction and immobilizing Pd nanoparticles. Sundry methods like FTIR, UV–Vis, ICP-AES, XRD, FE-SEM, WDX, TEM and EDX have been used for explaining the structure and morphology of the Pd NPs/RGO nanocatalyst. The outcomes indicate that the Pd (0) nanoparticles are completely spread on the functionalized GO surface. Pd NPs/RGO showed excellent catalytic performance as a recyclable nanocatalyst in Suzuki-Miyaura reactions with high yields. Moreover, the recycled nanocatalyst showed no considerable loss in its activity.

Control of the coordination structure of organometallic palladium complexes in an apo-ferritin cage

We report the preparation of organometallic Pd(allyl) dinuclear complexes in protein cages of apo-Fr by reactions with [Pd(allyl)Cl]2 (allyl = η3-C3H5). One of the dinuclear complexes is converted to a trinuclear complex by replacing a Pd-coordinated His residue to an Ala residue. These results suggest that multinuclear metal complexes with various coordination structures could be prepared by the deletion or introduction of His, Cys, and Glu at appropriate positions on protein surface. Copyright

Suzuki–Miyaura reaction by heterogeneously supported Pd nanoparticles on thio-modified multi walled carbon nanotubes as efficient nanocatalyst

The palladium (Pd) supported on thio-modified multi walled carbon nanotubes (MWCNTs/CC-SH/Pd) was utilized as a useful and reusable nanocatalyst in Suzuki–Miyaura coupling reactions. The catalyst was really efficient for the Suzuki–Miyaura reaction of aryl halides (Ar–I, Ar–Br, Ar–Cl) with phenylboronic acid and conversion was good in most cases. The aryl iodides and aryl bromides reactions take place at room temperature, while reaction of aryl chlorides occurs at temperature of 80 °C. The products yields ranged between70% and 96%. The catalyst indicated excellent constancy and could be recycled and reused up to four cycles with no considerable change in its catalytic behavior.

Open-vessel microwave-promoted Suzuki reactions using low levels of palladium catalyst: Optimization and scale-up

Representative Suzuki couplings in water using low catalyst concentrations in conjunction with microwave heating have been transferred from sealed-vessel to open-vessel reaction conditions. They have then been scaled-up to the mole scale using a dedicated multimode microwave apparatus. The reactions are complete within 20 min of heating at reflux.

Synthesis, microwave-promoted catalytic activity in Suzuki-Miyaura cross-coupling reactions and antimicrobial properties of novel benzimidazole salts bearing trimethylsilyl group

A mixture of benzimidazole salts (2-7), Pd(OAc)2 and K 2CO3 in DMF-H2O catalyzes the Suzuki-Miyaura cross-coupling reactions promoted by microwave irradiation resulting in high yield within a short time. In particular, the yield of the Suzuki-Miyaura reactions with aryl bromides was found to be nearly quantitative. The synthesized benzimidazole salts (2-7) were identified by 1H- 13C, NMR, IR spectroscopic methods and microanalysis. The molecular structure of 1 was determined by X-ray crystallography. The antibacterial and antifungal activities of the novel benzimidazole derivatives (1-7) were also tested against standard strains.